Drug Trials Snapshot: SKYTROFA

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The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

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Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.

Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the SKYTROFA Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).

Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).

SKYTROFA (Lonapegsomatropin-tcgd)
(sky-TRO-fuh)
Ascendis Pharma, Inc.
Original Approval date: August 25, 2021

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DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

SKYTROFA is a human growth hormone for the treatment of children 1 year and older who weigh at least 11.5 kilograms and are not growing because they have growth hormone deficiency (GHD).

GHD is a condition in which the body does not produce enough growth hormone (GH). Symptoms of GHD in children include poor growth and short stature.

How is this drug used?

SKYTROFA is given as an injection under the skin (subcutaneous) once weekly.

Who participated in the clinical trials?

The FDA approved SKYTROFA based on one clinical trial (Trial NCT02781727) of 161 patients with growth hormone deficiency and short stature. The trial was conducted at 54 sites in 14 countries: Armenia, Australia, Belarus, Bulgaria, Georgia, Greece, Italy, New Zealand, Poland, Romania, Russia, Turkey, Ukraine, and the United States. This trial was used to assess efficacy and safety.

Who participated in the trials?

Table 1 summarizes the percentage of patients by sex.

Table 1. Baseline Demographics by Sex

Sex	Number of Patients	Percentage
Male	132	82
Female	29	18

Source: Adapted from FDA Review

Table 2 summarizes the percentage of subjects by race.

Table 2. Baseline Demographics by Race for Subjects in the Trial

Race	Number of Patients	Percentage
White	152	94
Black or African American	3	2
Asian	1	1
All other	5	3

Source: Adapted from FDA Review

Table 3 summarizes participants by age.

Table 3. Baseline Demographics by Age for Subjects in the Trial

Age	Number of Patients	Percentage
<6 years	39	24
≥6 years	122	76

Source: Adapted from FDA Review

What are the benefits of this drug?

In a clinical trial, children who were treated with SKYTROFA once weekly had growth that was similar to children treated with an approved human growth hormone injection given once daily.

What are the benefits of this drug (results of trials used to assess efficacy)?

Efficacy results from the trial are presented in Table 4. The primary endpoint was the annualized height velocity, which is the change in standing height over a period of one year. The secondary endpoint was the change in standard deviation scores of height from baseline (a number used to tell how different is the child’s height from the average expected height of a child of similar age and sex).

Table 4. Annualized Height Velocity at Week 52 in Pediatric Treatment-Naïve Subjects with Growth Hormone Deficiency

Parameter	Once-Weekly SKYTROFA	Once-Daily SOMATROPIN
Annualized height velocity (cm/year)	11.2	10.3
Height SDS, baseline	-2.9	-3
Height SDS, change from baseline	1.1	0.96

Source: Adapted from FDA Review
Abbreviations: SDS, standard deviation score

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

• Sex: SKYTROFA worked similarly in male and female children.
• Race: The number of patients of races other than White was small; therefore, differences in how SKYTROFA worked among races could not be determined.
• Age: SKYTROFA worked similarly in all ages of children that were studied.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The subgroup analyses of the primary endpoint are presented in Table 5.

Table 5. Annualized Height Velocity at Week 52 by Sex and Age

Subgroup	Annualized Height Velocity		Difference* (95% CI)
	SKYTROFA	SOMATROPIN
Sex
Male	10.67	9.93	0.70 (0.03, 1.42)
Female	11.79	11.20	0.68 (-0.042, 1.70)
Age group (years)
<6	12.41	10.82	1.11 (0.09, 2.36)
≥6 to 12	10.65	10.23	0.30 (-0.16, 1.32)

Source: Adapted from FDA Review
* Treatment differences and credible intervals may not match values of (treatment minus control) since estimates include relevance of outcomes from other subgroups.
Abbreviations: CI, credible interval

What are the possible side effects?

SKYTROFA may cause serious side effects including:

• Allergic reactions
• Increased risk of cancer that is already present or new cancer
• New or worsening high blood sugar
• Increased intracranial pressure (pressure in the skull)
• Body fluid retention
• Decreased adrenal and thyroid gland function
• Slipped capital femoral epiphysis (“ball part” of the top of the thigh bone slips at the growth plate)
• Worsening of scoliosis (sideways curvature of the spine) that is already present
• Inflammation of pancreas
• Loss of fat tissue at the injection site

The most common side effects include viral infections, fever, cough, nausea, vomiting, hemorrhage, diarrhea, abdominal pain, arthralgia, arthritis, and increased blood phosphate levels.

What are the possible side effects?

Table 6 shows the frequency of side effects occurring in ≥5% of patients treated with SKYTROFA and more frequently than in somatropin-treated patients.

Table 6. Side Effects Occurring in ≥5% SKYTROFA-Treated Pediatric Patients and More Frequently Than in Somatropin-Treated Pediatric Patients (52 Weeks of Treatment)

Side Effect	Daily Somatropin (N=56) n (%)	SKYTROFA (N=105) n (%)
Infection, viral	6 (11%)	16 (15%)
Pyrexia	5 (9%)	16 (15%)
Cough	4 (7%)	11 (11%)
Nausea and vomiting	4 (7%)	11 (11%)
Hemorrhage*	1 (2%)	7 (7%)
Diarrhea	3 (5%)	6 (6%)
Abdominal pain	2 (4%)	6 (6%)
Arthralgia and arthritis†	1 (2%)	6 (6%)

Source: SKYTROFA Prescribing Information
* Hemorrhage in the SKYTROFA treatment grouping included epistaxis (3), contusion (2), petechiae (1), and eye hemorrhage (1)
† Arthralgia and arthritis in the SKYTROFA treatment group included arthralgia (5) and reactive arthritis (1).
Abbreviations: N, total number of patients in the group; n, number of patients with the side effect, %, percent of patients with the side effect

Were there any differences in side effects of the clinical trials among sex, race, and age?

• Sex: The occurrence of side effects was similar in male and female children.
• Race: The number of patients of races other than White was small; therefore, differences in side effects among races could not be determined.
• Age: The occurrence of side effects was similar in all ages studied.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Table 7. Overview of Side Effects by Sex, Race, and Age in Pediatric Patients with Growth Hormone Deficiency, Trial NCT02781727, Safety Population

Demographic Variable	SKYTROFA N=105		Somatropin N=56
	All Grades n/Ns (%)	Grade 3 n/Ns (%)	All Grades n/Ns (%)	Grade 3 n/Ns (%)
Sex, n (%)
Female	16/19 (84.2)	0/19 (0)	6/10 (60.0)	0/10 (0)
Male	65/86 (75.6)	1/86 (1.2)	33/46 (71.7)	0/46 (0)
Race, n (%)
Asian	1/1 (100)	0/1 (0)	0/0 (NA)	0/0 (NA)
Black or African American	2/2 (100)	0/2 (0)	1/1 (100)	0/1 (0)
White	76/100 (76.0)	1/100 (1.0)	35/52 (67.3)	0/52 (0)
All others	2/2 (100)	0/2 (0)	3/3 (100)	0/3 (0)
Age group, n (%)
<6 years	20/25 (80.0)	0/25 (0)	10/14 (71.4)	0/14 (0)
≥6 years	61/80 (76.2)	1/80 (1.2)	29/42 (69.0)	0/42 (0)

Source: FDA reviewer’s analysis
Abbreviation: N, number of patients in the safety population; n, number of patients with given characteristic; Ns, total number of patients in each category; NA, not applicable

DEMOGRAPHICS SNAPSHOT

Figure 1 summarizes how many male and female children were enrolled in the clinical trial.

Figure 1. Baseline Demographics by Sex

Source: Adapted from FDA Review

Figure 2 summarizes the percentage of participants by race.

Figure 2. Baseline Demographics by Race

Source: Adapted from FDA Review

Figure 3 summarizes participants by age.

Figure 3. Baseline Demographics by Age

Source: Adapted from FDA Review

Figure 4 summarizes participants by ethnicity.

Figure 4. Baseline Demographics by Ethnicity

Source: Adapted from FDA Review

How were the trials designed?

The benefits and side effects of SKYTROFA were evaluated in a clinical trial. Pediatric patients 3 to 12 years old were assigned at random to weekly SKYTROFA or another daily approved growth hormone for 52 weeks.

The benefit of SKYTROFA was assessed by measuring the annualized height velocity (change in standing height over 1 year) and comparing it to the once daily human growth hormone group.

How were the trials designed?

There was one multinational, controlled trial that provided data to support the approval of SKYTROFA. Patients 3 to 12 years old with short stature due to GHD were randomized to once-weekly SKYTROFA or to another approved once daily growth hormone for a total of 52 weeks.

The height gain at Week 52 was measured in each group and compared.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

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